1. Field of the Invention
The present invention relates to the field of medical prevention and treatment of a neuroinjury; in particular, relates to the prevention and treatment of HIV (Human immunodeficiency virus) infection and HIV-associated neurocognitive disorders (HAND).
2. Discussion of the Background
Currently there are several antiviral drugs for the treatment of HIV/AIDS. However, one of the main problems with antiviral drugs is the mutation of the virus and the HIV virus is not an exception. Some treatments were developed to extend the life of the person infected with the virus. For example one of the treatments is called HAART (Highly Active Antiretroviral Therapy), which is a treatment to suppress HIV viral replication and the progression of HIV disease. HAART is defined as treatment that comprises at least three active anti-retroviral medications (ARV's), typically two nucleoside or nucleotide reverse transcriptase inhibitors (NRTI's) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor (PI) or another NRTI called abacavir (Ziagen).
In addition there is a concern for HIV replication stimulated by inflammatory mediators, such as cytokines and chemokines. Therefore there is a major need to identify a compound that can prevent synthesis and liberation of proinflammatory cytokines and chemokines.
Further in the post-HAART era, HIV-associated neurocognitive disorders (HAND) have become the most common neurologic complication of AIDS, affecting approximately 40-60% of HIV-infected patients. HAND is an encephalopathy induced by HIV-1 infection and fueled by immune activation of T-lymphocytes and macrophages. These activated cells have the capability to enter the brain and secrete neurotoxins of both host and viral origin affecting brain cells such as glial cells and neurons. There is a major need to identify a compound that can prevent or alleviate the damaging effects following HIV-1 infection in the brain.
Several studies, as disclosed in US Patent Application 2009/0291976 and US Patent Application 2011/0015186, hereby included by reference, have identified a non-toxic compound called 4R-cembranoid (4R), a cyclic diterpenoid from the family of cembranoids, a natural product found in tobacco leaves and flowers that readily penetrates into the brain and has demonstrated anti-apoptotic, anti-inflammatory, and neuroprotective properties:                Neuroprotection: 4R protects the brain against N-methyl-D-aspartate (NMDA)-induced excitotoxicity. This was extensively studied in ex viva (brain slices) and briefly in vivo (Ferchmin et al., 2005). U.S. Pat. No. 6,204,289 B1, Issued: Mar. 20 2001        Anti-apoptotic: 4R stimulates certain NMDA receptors activating a prosurvival and anti-apoptotic process which involves increase of intracellular calcium, activation of the PI3-Kinase/Akt cascade followed by GSK-3beta inactivation (Ferchmin et al., 2005). U.S. patent application Ser. No. 12/308,293 (pending)        Anti-inflammatory: 4R inhibits COX with an IC50 lower than acetylsalicylic acid (Olsson et al., 1993).        
Therefore is a need to identify a effective dose of a compound that can diminish inflammatory mediators and prevent or alleviate the damaging effects following HIV-1 infection in the brain.